ERIBULIN MESYLATE

The pharmacokinetics (PK) of eribulin is linear with a mean elimination half-life of approximately 40 hours, a mean volume of distribution of 43 L/m 2 to 114 L/m 2 and mean clearance of 1.16 L/hr/m 2 to 2.42 L/hr/m 2 over the dose range of 0.25 mg/m 2 to 4.0 mg/m 2 . The human plasma protein binding of eribulin at concentrations of 100 ng/mL to 1,000 ng/mL ranges from 49% to 65%. Eribulin exposure after multiple dosing is comparable to that following a single dose. No accumulation of eribulin is...

14.1 Metastatic Breast Cancer Study 1 was an open-label, randomized, multicenter trial of 762 patients with metastatic breast cancer who received at least two chemotherapeutic regimens for the treatment of metastatic disease and experienced disease progression within 6 months of their last chemotherapeutic regimen. Patients were required to receive prior anthracycline- and taxane-based chemotherapy for adjuvant or metastatic disease. Patients were randomized (2:1) to receive eribulin mesylate (n=508) or a single agent therapy selected prior to randomization (control arm, n=254). Randomization ...

The most common adverse reactions (≥25%) in metastatic breast cancer were neutropenia, anemia, asthenia/fatigue, alopecia, peripheral neuropathy, nausea, and constipation. ( 6.1 ) The most common adverse reactions (≥25%) in liposarcoma and leiomyosarcoma were fatigue, nausea, alopecia, constipation, peripheral neuropathy, abdominal pain, and pyrexia. The most common (≥5%) Grade 3 to 4 laboratory abnormalities in liposarcoma and leiomyosarcoma were neutropenia, hypokalemia, and hypocalcemia. ( 6....

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Neutropenia : Monitor peripheral blood cell counts and adjust dose as appropriate. ( 5.1 ) Peripheral Neuropathy : Monitor for signs of neuropathy. Manage with dose delay and adjustment. ( 5.2 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception. ( 5.3 , 8.1 , 8.3 ) QT Prolongation : Monitor for prolonged QT intervals in patients with congestive heart failure, bradyarrhythmias, drugs known t...

7 DRUG INTERACTIONS 7.1 Effects of Other Drugs on Eribulin Mesylate No drug-drug interactions are expected with CYP3A4 inhibitors, CYP3A4 inducers or P‑glycoprotein (P-gp) inhibitors. Clinically meaningful differences in exposure (AUC) were not observed in patients with advanced solid tumors when eribulin mesylate was administered with or without ketoconazole (a strong inhibitor of CYP3A4 and a P-...